ABSTRACT
The phylogeny and divergence timing of the Neoavian radiation remain controversial despite recent progress. We analyzed the genomes of 124 species across all Neoavian orders, using data from 25,460 loci spanning four DNA classes, including 5,756 coding sequences, 12,449 conserved nonexonic elements, 4,871 introns, and 2,384 intergenic segments. We conducted a comprehensive sensitivity analysis to account for the heterogeneity across different DNA classes, leading to an optimal tree of Neoaves with high resolution. This phylogeny features a novel Neoavian dichotomy comprising two monophyletic clades: a previously recognized Telluraves (land birds) and a newly circumscribed Aquaterraves (waterbirds and relatives). Molecular dating analyses with 20 fossil calibrations indicate that the diversification of modern birds began in the Late Cretaceous and underwent a constant and steady radiation across the KPg boundary, concurrent with the rise of angiosperms as well as other major Cenozoic animal groups including placental and multituberculate mammals. The KPg catastrophe had a limited impact on avian evolution compared to the Paleocene-Eocene Thermal Maximum, which triggered a rapid diversification of seabirds. Our findings suggest that the evolution of modern birds followed a slow process of gradualism rather than a rapid process of punctuated equilibrium, with limited interruption by the KPg catastrophe. This study places bird evolution into a new context within vertebrates, with ramifications for the evolution of the Earth's biota.
Subject(s)
Fossils , Magnoliopsida , Pregnancy , Female , Animals , Magnoliopsida/genetics , Placenta , Phylogeny , Birds/genetics , Mammals/genetics , DNA, Mitochondrial/genetics , Biological EvolutionABSTRACT
Estimating transmission rates is a challenging yet essential aspect of comprehending and controlling the spread of infectious diseases. Various methods exist for estimating transmission rates, each with distinct assumptions, data needs, and constraints. This study introduces a novel phylogenetic approach called transRate, which integrates genetic information with traditional epidemiological approaches to estimate inter-population transmission rates. The phylogenetic method is statistically consistent as the sample size (i.e. the number of pathogen genomes) approaches infinity under the multi-population susceptible-infected-recovered model. Simulation analyses indicate that transRate can accurately estimate the transmission rate with a sample size of 200 ~ 400 pathogen genomes. Using transRate, we analyzed 40,028 high-quality sequences of SARS-CoV-2 in human hosts during the early pandemic. Our analysis uncovered significant transmission between populations even before widespread travel restrictions were implemented. The development of transRate provides valuable insights for scientists and public health officials to enhance their understanding of the pandemic's progression and aiding in preparedness for future viral outbreaks. As public databases for genomic sequences continue to expand, transRate is increasingly vital for tracking and mitigating the spread of infectious diseases.
Subject(s)
COVID-19 , Phylogeny , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/transmission , COVID-19/epidemiology , COVID-19/virology , Pandemics , Communicable Diseases/transmission , Communicable Diseases/epidemiology , Genome, ViralABSTRACT
BACKGROUND: Resolving the phylogeny of rapidly radiating lineages presents a challenge when building the Tree of Life. An Old World avian family Prunellidae (Accentors) comprises twelve species that rapidly diversified at the Pliocene-Pleistocene boundary. RESULTS: Here we investigate the phylogenetic relationships of all species of Prunellidae using a chromosome-level de novo assembly of Prunella strophiata and 36 high-coverage resequenced genomes. We use homologous alignments of thousands of exonic and intronic loci to build the coalescent and concatenated phylogenies and recover four different species trees. Topology tests show a large degree of gene tree-species tree discordance but only 40-54% of intronic gene trees and 36-75% of exonic genic trees can be explained by incomplete lineage sorting and gene tree estimation errors. Estimated branch lengths for three successive internal branches in the inferred species trees suggest the existence of an empirical anomaly zone. The most common topology recovered for species in this anomaly zone was not similar to any coalescent or concatenated inference phylogenies, suggesting presence of anomalous gene trees. However, this interpretation is complicated by the presence of gene flow because extensive introgression was detected among these species. When exploring tree topology distributions, introgression, and regional variation in recombination rate, we find that many autosomal regions contain signatures of introgression and thus may mislead phylogenetic inference. Conversely, the phylogenetic signal is concentrated to regions with low-recombination rate, such as the Z chromosome, which are also more resistant to interspecific introgression. CONCLUSIONS: Collectively, our results suggest that phylogenomic inference should consider the underlying genomic architecture to maximize the consistency of phylogenomic signal.
Subject(s)
Gene Flow , Genomics , Songbirds , Phylogeny , Genomics/methods , GenomeABSTRACT
Troponin T1 (TNNT1) plays a crucial role in muscle contraction but its role in cancer, particularly in kidney renal clear cell carcinoma (KIRC), is not well-understood. This study explores the expression, clinical significance and biological functions of TNNT1 in various cancers, with an emphasis on its involvement in KIRC. We analysed TNNT1 expression in cancers using databases like TCGA and GTEx, assessing its prognostic value, mutation patterns, methylation status and functional implications. The study also examined TNNT1's effect on the tumour microenvironment and drug sensitivity in KIRC, complemented by in vitro TNNT1 knockdown experiments in KIRC cells. TNNT1 is overexpressed in several cancers and linked to adverse outcomes, showing frequent upregulation mutations and abnormal methylation. Functionally, TNNT1 connects to muscle and cancer pathways, affects immune infiltration and drug responses, and its overexpression in KIRC is associated with advanced disease and reduced survival. Knocking down TNNT1 curbed KIRC cell growth. TNNT1's aberrant expression plays a significant role in tumorigenesis and immune modulation, highlighting its value as a prognostic biomarker and a potential therapeutic target in KIRC and other cancers. Further studies are essential to understand TNNT1's oncogenic mechanisms in KIRC.
Subject(s)
Carcinogenesis , Carcinoma, Renal Cell , Gene Expression Regulation, Neoplastic , Kidney Neoplasms , Troponin T , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinogenesis/genetics , Carcinogenesis/immunology , Carcinogenesis/pathology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Cell Proliferation , DNA Methylation , Immunomodulation/genetics , Kidney Neoplasms/genetics , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Mutation/genetics , Prognosis , Troponin T/metabolism , Troponin T/genetics , Tumor Microenvironment/immunologyABSTRACT
Horticultural crops comprising fruit, vegetable, ornamental, beverage, medicinal and aromatic plants play essential roles in food security and human health, as well as landscaping. With the advances of sequencing technologies, genomes for hundreds of horticultural crops have been deciphered in recent years, providing a basis for understanding gene functions and regulatory networks and for the improvement of horticultural crops. However, these valuable genomic data are scattered in warehouses with various complex searching and displaying strategies, which increases learning and usage costs and makes comparative and functional genomic analyses across different horticultural crops very challenging. To this end, we have developed a lightweight universal search engine, HortGenome Search Engine (HSE; http://hort.moilab.net), which allows for the querying of genes, functional annotations, protein domains, homologs, and other gene-related functional information of more than 500 horticultural crops. In addition, four commonly used tools, including 'BLAST', 'Batch Query', 'Enrichment analysis', and 'Synteny Viewer' have been developed for efficient mining and analysis of these genomic data.
ABSTRACT
The origins of late-life depression are multifaceted and remain challenging to fully understand. While the traditional monoamine neurotransmitter hypothesis provides some insights, it falls short in explaining the disease's onset and progression, leaving treatments often less than optimal. There is an emergent need to uncover new underlying mechanisms. Among these, the "inflammation hypothesis" has been gaining traction in scientific discussions regarding late-life depression. There is compelling evidence linking inflammation processes to the emergence of this form of depression. This review delves into the nuanced relationship between inflammation and late-life depression, emphasizing the pivotal role and implications of inflammation in its pathogenesis. Changes in Ca2+ homeostasis, cytokine levels, brain-derived neurotrophic factor (BDNF), white cell ratios, and the involvement of the NOD-, LRR-, and Pyrin domain-containing protein 3 (NLRP3) inflammasome have all been suggested as potential biomarkers that tie inflammation to late-life depression. Furthermore, factors such as aging-induced DNA damage, oxidative stress, mitochondrial impairments, disruptions in the hypothalamic-pituitary-adrenal axis, activated microglia and associated neuroinflammation, as well as the gut-brain axis dynamics, could serve as bridges between inflammation and depression. Deepening our understanding of these connections could usher in innovative anti-inflammatory treatments and strategies for late- life depression.